Atypical processing of uncertainty in individuals at risk for psychosis

Current theories of psychosis highlight the role of abnormal learning signals, i.e., prediction errors (PEs) and uncertainty, in the formation of delusional beliefs. We employed computational analyses of behaviour and functional magnetic resonance imaging (fMRI) to examine whether such abnormalities are evident in clinical high risk (CHR) individuals. Non-medicated CHR individuals (n = 13) and control participants (n = 13) performed a probabilistic learning paradigm during fMRI data acquisition. We used a hierarchical Bayesian model to infer subject-specific computations from behaviour – with a focus on PEs and uncertainty (or its inverse, precision) at different levels, including environmental ‘volatility’ – and used these computational quantities for analyses of fMRI data. Computational modelling of CHR individuals’ behaviour indicated volatility estimates converged to significantly higher levels than in controls. Model-based fMRI demonstrated increased activity in prefrontal and insular regions of CHR individuals in response to precision-weighted low-level outcome PEs, while activations of prefrontal, orbitofrontal and anterior insula cortex by higher-level PEs (that serve to update volatility estimates) were reduced. Additionally, prefrontal cortical activity in response to outcome PEs in CHR was negatively associated with clinical measures of global functioning. Our results suggest a multi-faceted learning abnormality in CHR individuals under conditions of environmental uncertainty, comprising higher levels of volatility estimates combined with reduced cortical activation, and abnormally high activations in prefrontal and insular areas by precision-weighted outcome PEs. This atypical representation of high- and low-level learning signals might reflect a predisposition to delusion formation

Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G 7 E), however, so far, thorough replication of findings is rare and G 7 E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G 7 E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G 7 E in schizophrenia. While such investigations are now well underway, new challenges emerge for G 7 E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. \ua9 2014 The Author

Attention problems and language development in preterm low-birth-weight children: Cross-lagged relations from 18 to 36 months

<p>Abstract</p> <p>Background</p> <p>Research has highlighted a series of persistent deficits in cognitive ability in preterm low-birth-weight children. Language and attention problems are among these deficits, although the nature of the relation between attention and language in early development is not well known. This study represents a preliminary attempt to shed light on the relations between attention problems and language development in preterm low-birth-weight children.</p> <p>Methods</p> <p>The aim of this study was to analyse reciprocal influences between language and attention problems from 18 to 36 months. We used maternal reports on attention problems and language ability referring to a sample of 1288 premature low-birth-weight infants, collected as part of the Norwegian Mother and Child Cohort Study (MoBa). A sample of children born full-term was used as the control group (N = 37010). Cross-lagged panel analyses were carried out to study reciprocal influences between attention problems and language.</p> <p>Results</p> <p>Language ability at 18 months did not significantly predict attention problems at 36 months, adjusting for attention problems at 18 months. Attention problems at 18 months significantly predicted changes in language ability from 18 to 36 months, pointing to a precursor role of attention in relation to language in children born preterm. Gender, age corrected for prematurity, and mother's education emerged as important covariates.</p> <p>Conclusions</p> <p>Preliminary evidence was found for a precursor role of early attention problems in relation to language in prematurity. This finding can contribute to a better understanding of the developmental pathways of attention and language and lead to better management of unfavourable outcomes associated with co-morbid attention and language difficulties.</p